Deleterious role of anti-high mobility group box 1 monoclonal antibody in retinal ischemia-reperfusion injury

Purpose: To investigate the effect of anti-high mobility group box 1 (HMGB1) monoclonal antibody (mAb) against ischemia-reperfusion injury in the rat retina. Materials and Methods: Retinal ischemia was induced by increasing and then maintaining intraocular pressure at 130 mmHg for 45min. An intraperitoneal injection of anti-HMGB1 mAb was administered 30min before ischemia. Retinal damage was evaluated at 7 days after the ischemia. Immunohistochemistry and image analysis were used to measure changes in the levels of reactive oxygen species (ROS) and the localization of anti-HMGB1 mAb. Dark-adapted full-field electroretinography (ERG) was also performed. Results: Pretreatment with anti-HMGB1 mAb significantly enhanced the ischemic injury of the retina. HMGB1 expression increased at 612h after ischemia in the retina. After the ischemia, production of ROS was detected in retinal cells. However, pretreatment with anti-HMGB1 mAb increased the production of ROS. On the seventh postoperative day, the amplitudes of both the ERG a-and b-waves were significantly higher in the vehicle group than in the groups pretreated with anti-HMGB1 mAb. Conclusions: The current in vivo model of retinal injury demonstrated that anti-HMGB1 mAb plays a large deleterious role in ischemia-reperfusion injury. In order to develop neuroprotective therapeutic strategies for acute retinal ischemic disorders, further studies on anti-HMGB1 mAb function are needed.